Structural investigations of human serum albumin, transferrin, the beta-chain of haptoglobin, the group-specific protein and ceruloplasmin are being conducted in order to detect amino acid alterations or sequence rearrangements in inherited variants of these molecules. Subunit characterization in the serum proteins will provide evidence for the number of structural genes controlling the conformation of each protein. Computer analyses ultimately will be utilized to detect and evaluate relationships among proteins, which we have studied, in addition to sequences performed in other laboratories, that are too remote to be recognized visibly by their unchanged amino acids. When enough sequence information is available the phylogenetic tree of families of proteins can be constructed. In vitro systems will be utilized to characterize the mechanisms involved in the synthesis processing of serum proteins. Initial studies will be conducted with (1) activated liver cells and (2) human hepatoma cell lines. Eventually, it is expected that the structural genes controlling the synthesis of these proteins (or their subunits) will be mapped on chromosomes.